Prof. Lee, Young-Sam
University of Texas at Austin, PhD.
Genome is the genetic material of an organism, composed of nucleic acids. In order for sustainability of species with its own traits, living organisms have evolved the sophisticated 3R process; DNA Replication, Repair, and Recombination, which keep genomic integrity. However, DNA damage environmental mutagens and inevitable consequence of cellular metabolism and/or impairment of the 3R process cause genome instability, eventually leads to cellular senescence.
The main question in our group is whether physiological degenerative changes in senescent cells could be attenuated or even reversed to their initial states by genetic restoration. To address the question, we are striving to understand mechanisms of genome maintenance and developing means for elevating DNA repair capability to overcome genetic instability and furthermore to restore senescence. With structural information determined by X-ray crystallography and functional characterization from reconstituted system with purified components, we are focusing on investigating the structural-functional relationship as well as phenotypic-genotypic connection of machinery involved in the 3R process. Based on the knowledge of the regulatory mechanism of the 3R and senescence, we are also searching for small molecules or novel genetic factors targeting genomic integrity and functional restoration of cellular senescence.
Our studies will help to set a solid fundamental foundation to understand the primal curiosity, human aging and longevity.
Our objective is to restore cellular function in senescent stage by genome maintenance-based approach
To pursue the objective, we carry out the following research topics:
1. Interpret the structure based function in DNA replication utilizing physiologically relevant damaged DNA substrates.
2. Investigate the role of RNA transcripts (e.g. long noncoding RNAs) and their binding factors in DNA repair regarding cellular senescence.
3. Identify small molecules/genetic factors inducing DNA repair capability and physiological restoration of senescent cells. Figure out the mechanism of action in the restoration by the selected factors.
- How a homolog of high-fidelity replicases conducts mutagenic DNA synthesis. Nature Struct Mol Biol, 22:298. 2015
- Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass. PNAS USA, 111:2954. 2014
- Each monomer of the dimeric accessory protein for human mitochondrial DNA polymerase has a distinct role in conferring processivity. J Biol Chem, 285:1490. 2010
- Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Cell, 139:312. 2009